- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05106309
Pharmacokinetics of CVL-231 Following Single Oral Administration of Modified- and Immediate-release Formulations in Fasted and Fed Healthy Participants
April 25, 2022 updated by: Cerevel Therapeutics, LLC
A Phase 1, Open-label Trial to Evaluate the Pharmacokinetics of CVL-231 Following Single Oral Administration of Modified- and Immediate-release Formulations Under Fasted and Fed Conditions in Healthy Participants
A 2-part, crossover design, open-label treatment trial with 4 periods, 4 sequences (Part A) to evaluate MR formulations of CVL-231 and a 2 periods, 2 sequences (Part B) to understand effect of food on CVL-231 exposures from an MR formulation.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
CVL-231 is a muscarinic acetylcholine receptor (mAChR) activator that selectively binds to the M4 muscarinic receptor subtype (M4 mAChR) and is being developed for treatment of psychosis in schizophrenia.
Part A of this 2-part trial will investigate the PK of CVL-231 in healthy participants following a single oral dose of CVL-231 as 3 modified-release (MR) formulations with different release rates and an immediate-release (IR) formulation under fasted conditions.
Upon selection of an MR formulation with appropriate PK characteristics, the effect of food on the PK of CVL-231 and its metabolite following single oral doses of the selected MR formulation may be evaluated in Part B.
Study Type
Interventional
Enrollment (Actual)
16
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Arizona
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Tempe, Arizona, United States, 85283
- Celerion Inc.
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Women of nonchildbearing potential and men 18 to 55 years, inclusive.
- Healthy as determined by medical evaluation, including medical and psychiatric history, physical and neurological examinations, ECG, vital sign measurements, and laboratory test results, as evaluated by the investigator.
- Body mass index of 18.5 to 30.0 kg/m2 and a total body weight >50 kg (110 lbs).
- Sexually active men with a pregnant or a nonpregnant partner of childbearing potential must agree to comply with protocol contraception requirements during treatment and through 7 days post dose. In addition, male participants should not donate sperm for a minimum of 7 days following the last dose of IMP.
- Capable of giving signed informed consent.
- Ability, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements.
Exclusion Criteria:
- Current history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, endocrine, hematological, immunological, or neurological disease that, in the opinion of the investigator or medical monitor, could compromise either participant safety or the results of the trial.
- Current or past personal or family history of any psychiatric disorder as classified by DSM-5 criteria.
- Epilepsy or a history of seizures except for a single seizure episode, eg, a childhood febrile seizure, a seizure related to trauma or alcohol withdrawal, or an unexplained loss of consciousness.
- History of moderate to severe substance or alcohol-use disorder (excluding caffeine) within 12 months prior to signing the ICF.
- Serious risk of suicide in the opinion of the investigator
- Receipt of SARS-CoV2 vaccine or booster within 28 days of dosing with CVL-231, or plan to receive SARS-CoV2 vaccination or booster from Screening through 5 days after last dose of CVL-231.
- Have recently been diagnosed with symptomatic COVID-19 or test positive for COVID-19 within 30 days prior to signing the ICF.
Either of the following:
- History of HIV, hepatitis B, or hepatitis C infection
- Positive result for HIV antibody, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody
- Positive drug screen for illicit drugs or a positive test for alcohol
- 12-lead ECG demonstrating pre-defined abnormalities at Screening and Day -1 based on local evaluation.
- Abnormal clinical laboratory tests or vital sign measurements at the Screening Visit and at Day -1 (check-in) for each period
- Known to be allergic or hypersensitive to the IMP or any of its components.
- Participation in any clinical trial within 90 days prior to signing the ICF.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions
Oral Dose
|
Tablets
Capsules
Capsules
Capsules
|
Experimental: Part B: Single doses of CVL-231 target release formulation under fasted and fed conditions
Oral Dose
|
Capsules
Capsules
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Primary Part A & B: Peak Plasma Concentration (Cmax) for CVL-231 and Metabolite (CV-0000364)
Time Frame: Up to 72 Hours in each period
|
Up to 72 Hours in each period
|
Primary Part A & B: Time to Maximum Concentration (Tmax) for CVL-231 and Metabolite (CV-0000364)
Time Frame: Up to 72 Hours in each period
|
Up to 72 Hours in each period
|
Primary Part A & B: Time prior to the first measurable (non-zero) concentration (Tlag) for CVL-231 and Metabolite (CV-0000364)
Time Frame: Up to 72 Hours in each period
|
Up to 72 Hours in each period
|
Primary Part A & B: Area under the plasma concentration-time curve from time 0 to the last measurable time point (AUClast) for CVL-231 and Metabolite (CV-0000364)
Time Frame: Up to 72 Hours in each period
|
Up to 72 Hours in each period
|
Primary Part A & B: Area under the plasma concentration-time curve from time zero to infinity (AUCinf) for CVL-231 and Metabolite (CV-0000364)
Time Frame: Up to 72 Hours in each period
|
Up to 72 Hours in each period
|
Primary Part A & B: Elimination half-life (t½) for CVL-231 and Metabolite (CV-0000364)
Time Frame: Up to 72 Hours in each period
|
Up to 72 Hours in each period
|
Primary Part A only: Dose normalized Cmax, derived by Cmax divided by the dose administered (Cmax/D) for CVL-231 and Metabolite (CV-0000364)
Time Frame: Up to 72 Hours in each period
|
Up to 72 Hours in each period
|
Primary Part A only: Dose normalized AUClast, derived by AUClast divided by the dose administered (AUClast/D) for CVL-231 and Metabolite (CV-0000364)
Time Frame: Up to 72 Hours in each period
|
Up to 72 Hours in each period
|
Primary Part A only: Dose normalized AUCinf, derived by AUCinf divided by the dose administered (AUCinf/D) for CVL-231 and Metabolite (CV-0000364)
Time Frame: Up to 72 Hours in each period
|
Up to 72 Hours in each period
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Secondary: Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)
Time Frame: Up to Day 14
|
Up to Day 14
|
|
Secondary: Incidence of clinically significant changes in electrocardiogram (ECG) results
Time Frame: Up to 72 Hours in each period
|
Assessment of clinically significant changes in QT intervals measured by 12-lead ECG recording after the participant has been supine and at rest for at least 3 minutes.
|
Up to 72 Hours in each period
|
Secondary: Incidence of clinically significant changes in clinical laboratory results
Time Frame: Up to 72 Hours in each period
|
Up to 72 Hours in each period
|
|
Secondary: Incidence of clinically significant changes in vital sign measurements
Time Frame: Up to 72 Hours in each period
|
Assessment of clinically significant changes in vital signs including temperature, systolic and diastolic blood pressure, and heart rate.
|
Up to 72 Hours in each period
|
Secondary: Incidence of clinically significant changes in physical and neurological examination results
Time Frame: Up to 72 Hours in each period
|
Up to 72 Hours in each period
|
|
Secondary: Clinically significant findings in suicidality assessed using the Columbia Suicide-Severity Rating Scale (C-SSRS)
Time Frame: Up to 72 Hours in each period
|
The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent."
The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide.
C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent).
|
Up to 72 Hours in each period
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 29, 2021
Primary Completion (Actual)
February 24, 2022
Study Completion (Actual)
February 24, 2022
Study Registration Dates
First Submitted
November 1, 2021
First Submitted That Met QC Criteria
November 1, 2021
First Posted (Actual)
November 3, 2021
Study Record Updates
Last Update Posted (Actual)
April 27, 2022
Last Update Submitted That Met QC Criteria
April 25, 2022
Last Verified
April 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CVL-231-1004
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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